Four separate theoretical projects that deal with biomolecular diffusion are planned. (1) Numerical methods will be developed to characterize the overall diffusional motion of flexible biomolecules, including effects due to interactions with other molecules. (2) The effects of binding site dynamics on diffusion-influenced reaction rates will be studied by use of analytic and numerical models. (3) Helix-coil transitions of polypeptides in water will be studied by computer simulation. (4) Methods for choosing the optimum reaction coordinate in multidimensional diffusional activated processes will be developed. The long-term objectives of this work are to provide a detailed understanding of and computational methods for the kinetics of such processes as hormone-receptor binding and substrate-binding or product-release from enzymes. Some of the methods to be developed will also facilitate the interpretation of data from experiments (e.g., NMR relaxation, fluorescence depolarization) that probe biomolecular diffusional motions.